Vascular delivery systems
AssigneeBen-Gurion University of the Negev Research and Development Authority
InventorsAyelet David, Gonen Ashkenasy, Yosi Shamay
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Abstract
The site-specific expression of selectins on endothelial cells of blood vessels during angiogenesis provides an opportunity to target anti-cancer drugs to the vascular endothelium to extend the range of the therapeutic effect. This invention describes an innovative drug targeting strategy for the selective delivery of the anticancer drugs to endothelial cells by means of polymer-drug conjugates modified with a carbohydrate ligand for the vascular selectins. A model chemotherapeutic drug, doxorubicin, and the E-selectin ligand, sLex, are attached to a biocompatible polymer (HPMA). The selective binding, cellular uptake, intracellular fate, and cell cytotoxicity of the polymer-bound drug are investigated in human endothelial cells.
Claims20
A polymer comprising repeating units
- wherein
- X is 2-hydroxypropyl;
- Y is a tripeptide selected from the group consisting of GGG and GGC, wherein the amide nitrogen shown in (b) is part of the initial G residue;
- J is a peptide targeting moiety having the sequence of SEQ ID NO:
- 2, wherein J is bonded to Y at the terminal G or C residue;
- Z is a drug optionally comprising a spacer;
- and
- W is an imaging agent optionally comprising a spacer;
- and
- wherein between about 50% and 99.95% of the total repeating units in the polymer are (a) or derivatives of (a);
- between 0.05% and 50% of the total repeating units in the polymer are (b), between about 0 to 50% of the total repeating units in the polymer are (c), and between 0 to 15% of the total repeating units in the polymer are (d).
Dependencies are inferred from the claim text.